"This ion channel becomes active during dehydration, switching on the neurons in a part of the brain called the hypothalamus, which instructs the body to act in order to maintain its fluid balance," says Charles Bourque. (Credit: limmurf/Flickr)

Scientists have identified the structure of a key protein in the brain that is involved with hydration and may help control body temperature.

The findings suggest the protein could be used as a target to develop treatments and diagnostic tests for health problems associated with the imbalance of bodily fluids, a condition commonly seen in hospital emergency departments.

“We have identified what we think is the first protein that could allow the brain to monitor physiological temperature and it is important because this protein contributes to how the brain detects heat and triggers adaptive responses such as thirst,” says Charles Bourque a researcher at the Centre for Research in Neuroscience at the Research Institute of the McGill University Health Centre.

“This protein, which is an ion channel, that regulates the flow of ions across the cell membrane, is thought to play a crucial role in balancing body fluids (water, blood, etc.) and sodium (salts) levels, and changes in its regulation could be involved in linking salt to hypertension, and provoking fluid retention following cardiac failure, sepsis, or brain trauma.”

Researchers are investigating how the brain controls osmoregulation—the maintenance of salt and water balance across membranes within the body’s fluids. Modification of osmoregulation can have major health consequences on humans. Indeed, sodium is necessary to regulate the water content in our body, as a result, high salt levels can damage kidneys and increase blood pressure.

Defects in the body’s fluid balance are among the most common reasons for being hospitalized when admitted to the emergency room. For example, hyponatremia is a disorder that occurs when the level of sodium in the blood is abnormally low. Sodium is an electrolyte that helps regulate the amount of water that’s in and around our cells.

When this happens, the body’s water levels rise, and brain cells begin to swell, leading to nausea, vomiting, and headaches—a common problem in older adults that can lead to changes in cognition and even seizures.

“Now that we have discovered the protein’s structure, we can try to understand how this ion channel is involved in conditions such as hyponatremia,” says first author and postodoctoral fellow Cristian Zaelzer. “This would give us tools to modify the channel’s mechanism of action and either prevent or treat the condition.”

The discovery, reported in Cell Reports, stems from previous work where researchers demonstrated that a gene called TRPV1 played an essential role in detecting changes in balancing the body’s fluids. Two years later, researchers discovered that the same gene was involved in detecting body temperature. However, the type of protein produced by the TRPV1 gene was still unknown.

“Collaborating with Dr. Bourque’s group led to identification of a long sought-after TRPV1 ion channel that functions in neurons, making them sense osmotic pressure and temperature,” senior coauthor Wolfgang Liedtke, associate professor of neurology, anesthesiology, and neurobiology at Duke University.

“This ion channel becomes active during dehydration, switching on the neurons in a part of the brain called the hypothalamus, which instructs the body to act in order to maintain its fluid balance. This can be achieved by triggering a sense of thirst, and also by the secretion of vasopressin—an antidiuretic hormone that acts to promote the retention of water by the kidneys—to maintain body fluid balance.”

“Interestingly, our work also shows that the ion channel is an alternate product of the gene TRPV1 that normally codes for the capsaicin receptor that detects hot chili peppers,” Bourque says. “It is like nature has engineered a salt receptor out of a pepper receptor.”